The Ewing family of tumors is a group of cancers that includes Ewing tumor of bone (“Ewing's sarcoma”), extraosseous Ewing tumors, primitive neuroectodermal tumors (PNET), and Askin tumors (PNET of the chest wall). These tumors are aggressive malignancies that occur mainly in the childhood through adolescent/young adult years. Over 85% of cases of Ewing family tumors result from a chromosomal translocation, which fuses the EWS gene on chromosome 22 to the FLI1 gene on chromosome 11. The EWS/FLI fusion protein functions in the pathogenesis of Ewing family of tumors by modulating the expression of target genes.
Among the Ewing family of tumors, Ewing's sarcoma is the second most common primary bone cancer affecting children and young adults and is also one of the most common soft tissue malignancies of this age group.
Despite advances in treatment of localized Ewing's sarcoma, almost all patients have asymptomatic metastatic disease at the time of diagnosis. The long-term survival for metastatic Ewing's sarcoma is less than 10%.
Doxorubicin is the current standard systemic therapy for these tumors. However, only 20% of sarcomas respond to this drug. Furthermore, the clinical utility of doxorubicin is limited by significant side-effects, in particular irreversible cardiac toxicity.
A significant unmet medical need exists for new therapeutic agents that are effective in the treatment of Ewing family tumors and lack untoward cardiac cytotoxicity.